Date: 2015-10-16
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of results in The Lancet Oncology
Company: Eisai (Japan)
Product: lenvatinib in combination with everolimus
Action
mechanism: tyrosine kinase inhibitor/kinase inhibitor. Lenvatinib is an oral molecular targeted agent that selectively inhibits the activities of several different molecules including vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), RET, KIT and platelet-derived growth factor receptors (PDGFR). It simultaneously inhibits VEGFR, FGFR and also RET which are especially involved in tumour angiogenesis and proliferation of thyroid cancer. This potentially makes lenvatinib the first TKI that simultaneously inhibits the kinase activities of FGFR 1-4 as well as VEGFR 1-3. It is currently under investigation as a treatment for thyroid, hepatocellular carcinoma (Phase III), non-small cell lung cancer (Phase II) and other solid tumour types. Discovered and developed by Eisai, lenvatinib received accelerated European Medicines Agency (EMA) review on the 31 July and was filed in Europe and the U.S. on 18 August 2014. The FDA granted approval to Lenvima® (lenvatinib) to treat patients with progressive, differentiated thyroid cancer (DTC) whose disease progressed despite receiving radioactive iodine therapy (radioactive iodine refractory disease) on February 13, 2015. Lenvatinib was granted orphan drug designation (ODD) for the treatment of follicular and papillary thyroid cancer by the European Commission in April 2013. Lenvatinib is currently indicated for the treatment of adult patients with progressive locally advanced or metastatic, differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI).
Disease: metastatic renal cell carcinoma (mRCC) following prior VEGF-targeted therapy
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On October 16, 2015, Eisai announced the publication of Phase II results of lenvatinib in The Lancet Oncology (Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial ). These results show lenvatinib, when used in combination with everolimus, demonstrates significantly improved progression-free survival (PFS) versus everolimus alone in people with metastatic renal cell carcinoma (mRCC) following prior VEGF-targeted therapy (14.6 months versus 5.5 months respectively (HR=0.40; 95% CI,0.24-0.68; p<0.001)). Further results from the study, published in The Lancet Oncology, show significant improvements in objective response rates (ORR) for the lenvatinib plus everolimus combination compared to everolimus alone (43% vs. 6%, p<0.0001) and for lenvatinib compared to everolimus alone (27% vs. 6%, p=0.0067). ORR is defined as the proportion of patients to see a tumour size reduction of a predefined amount for a minimum time period. One of the study's secondary endpoints shows that, in an updated analysis, lenvatinib plus everolimus extends overall survival, compared to everolimus alone (median OS 25·5, 95% CI 16·4 to NE and 15·4, 95% CI 11·8 to 19·6 months, respectively; HR 0·51, 95% CI 0·30 to 0·88; P=0·024). For lenvatinib in combination with everolimus, the most common treatment-emergent adverse events (TEAE) reported were diarrhoea, fatigue and decreased appetite. The most common TEAEs of Grade 3 or higher (Common Terminology Criteria for Adverse Events) included diarrhoea, fatigue and hypertension. Patients in the study were previously treated with a VEGF-targeted therapy and randomized 1:1:1 to receive lenvatinib (18 mg once a day) and everolimus (5 mg once a day), lenvatinib (24 mg once a day) or everolimus (10 mg once a day). Nearly all patients (99%) had received one prior VEGF-targeted therapy, 1% had received two prior VEGF-targeted therapies, and 18% had received prior immunotherapy treatment.
